The Transactional Conflict Problem

The transactional conflict problem arises in transactional systems whenever two or more concurrent transactions clash on a data item. While the standard solution to such conflicts is to immediately abort one of the transactions, some practical systems consider the alternative of delaying conflict resolution for a short interval, which may allow one of the transactions to commit. The challenge in the transactional conflict problem is to choose the optimal length of this delay interval so as to minimize the overall running time penalty for the conflicting transactions. In this paper, we propose a family of optimal online algorithms for the transactional conflict problem. Specifically, we consider variants of this problem which arise in different implementations of transactional systems, namely "requestor wins" and "requestor aborts" implementations: in the former, the recipient of a coherence request is aborted, whereas in the latter, it is the requestor which has to abort. Both strategies are implemented by real systems. We show that the requestor aborts case can be reduced to a classic instance of the ski rental problem, while the requestor wins case leads to a new version of this classical problem, for which we derive optimal deterministic and randomized algorithms. Moreover, we prove that, under a simplified adversarial model, our algorithms are constant-competitive with the offline optimum in terms of throughput. We validate our algorithmic results empirically through a hardware simulation of hardware transactional memory (HTM), showing that our algorithms can lead to non-trivial performance improvements for classic concurrent data structures

Preparation and structural properties of thin films and multilayers of the Heusler compounds Cu2MnAl, Co2MnSn, Co2MnSi and Co2MnGe

We report on the preparation of thin films and multilayers of the intermetallic Heusler compound CuMnAl, Co2MnSn, Co2MnSi and Co2MnGe by rf-sputtering on MgO and Al2O3 substrates. Cu2MnAl can be grown epitaxially with (100)-orientation on MgO (100) and in (110)-orientation on Al2O3 a-plane. The Co based Heusler alloys need metallic seedlayers to induce high quality textured growth. We also have prepared multilayers with smooth interfaces by combining the Heusler compounds with Au and V. An analysis of the ferromagnetic saturation magnetization of the films indicates that the Cu2MnAl-compound tends to grow in the disordered B2-type structure whereas the Co-based Heusler alloy thin films grow in the ordered L21 structure. All multilayers with thin layers of the Heusler compounds exhibit a definitely reduced ferromagnetic magnetization indicating substantial disorder and intermixing at the interfaces.Comment: 21 pages, 8 figure

Half-metallicity and Slater-Pauling behavior in the ferromagnetic Heusler alloys

Introductory chapter for the book "Halfmetallic Alloys - Fundamentals and Applications" to be published in the series Springer Lecture Notes on Physics, P. H. Dederichs and I. Galanakis (eds). It contains a review of the theoretical work on the half-metallic Heusler alloys.Comment: Introductory chapter for the book "Halfmetallic Alloys - Fundamentals and Applications" to be published in the series Springer Lecture Notes on Physics, P. H. Dederichs and I. Galanakis (eds

Slater-Pauling Behavior of the Half-Ferromagnetic Full-Heusler Alloys

Using the full-potential screened Korringa-Kohn-Rostoker method we study the full-Heusler alloys based on Co, Fe, Rh and Ru. We show that many of these compounds show a half-metallic behavior, however in contrast to the half-Heusler alloys the energy gap in the minority band is extremely small. These full-Heusler compounds show a Slater-Pauling behavior and the total spin-magnetic moment per unit cell (M_t) scales with the total number of valence electrons (Z_t) following the rule: M_t=Z_t-24. We explain why the spin-down band contains exactly 12 electrons using arguments based on the group theory and show that this rule holds also for compounds with less than 24 valence electrons. Finally we discuss the deviations from this rule and the differences compared to the half-Heusler alloys.Comment: 10 pages, 8 figures, revised figure 3, new text adde

Exposure to the Amino Acids Histidine, Lysine, and Threonine Reduces mTOR Activity and Affects Neurodevelopment in a Human Cerebral Organoid Model

Evidence of the impact of nutrition on human brain development is compelling. Previous in vitro and in vivo results show that three specific amino acids, histidine, lysine, and threonine, synergistically inhibit mTOR activity and behavior. Therefore, the prenatal availability of these amino acids could be important for human neurodevelopment. However, methods to study the underlying mechanisms in a human model of neurodevelopment are limited. Here, we pioneer the use of human cerebral organoids to investigate the impact of amino acid supplementation on neurodevelopment. In this study, cerebral organoids were exposed to 10 mM and 50 mM of the amino acids threonine, histidine, and lysine. The impact was determined by measuring mTOR activity using Western blots, general cerebral organoid size, and gene expression by RNA sequencing. Exposure to threonine, histidine, and lysine led to decreased mTOR activity and markedly reduced organoid size, supporting findings in rodent studies. RNA sequencing identified comprehensive changes in gene expression, with enrichment in genes related to specific biological processes (among which are mTOR signaling and immune function) and to specific cell types, including proliferative precursor cells, microglia, and astrocytes. Altogether, cerebral organoids are responsive to nutritional exposure by increasing specific amino acid concentrations and reflect findings from previous rodent studies. Threonine, histidine, and lysine exposure impacts the early development of human cerebral organoids, illustrated by the inhibition of mTOR activity, reduced size, and altered gene expression

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

The transactional conflict problem

The transactional conflict problem arises in transactional systems whenever two or more concurrent transactions clash on a data item. While the standard solution to such conflicts is to immediately abort one of the transactions, some practical systems consider the alternative of delaying conflict resolution for a short interval, which may allow one of the transactions to commit. The challenge in the transactional conflict problem is to choose the optimal length of this delay interval so as to minimize the overall running time penalty for the conflicting transactions. In this paper, we propose a family of optimal online algorithms for the transactional conflict problem. Specifically, we consider variants of this problem which arise in different implementations of transactional systems, namely "requestor wins'' and "requestor aborts'' implementations: in the former, the recipient of a coherence request is aborted, whereas in the latter, it is the requestor which has to abort. Both strategies are implemented by real systems. We show that the requestor aborts case can be reduced to a classic instance of the ski rental problem, while the requestor wins case leads to a new version of this classical problem, for which we derive optimal deterministic and randomized algorithms. Moreover, we prove that, under a simplified adversarial model, our algorithms are constant-competitive with the offline optimum in terms of throughput. We validate our algorithmic results empirically through a hardware simulation of hardware transactional memory (HTM), showing that our algorithms can lead to non-trivial performance improvements for classic concurrent data structures

'Break the Chains 2015' community-based HIV prevention campaign for men who have sex with men in Switzerland: non-randomised evaluation and cost analysis.

OBJECTIVES To study the implementation, effects and costs of Break the Chains, a community-based HIV prevention campaign for men who have sex with men (MSM) in Switzerland, from March to May 2015, which aimed to reduce early HIV transmission by promoting the campaign message to adopt short-term risk reduction followed by HIV testing. DESIGN Non-randomised evaluation and cost analysis. SETTING Gay venues in 11 of 26 cantons in Switzerland and national online media campaign. PARTICIPANTS MSM in online surveys (precampaign n=834, postcampaign n=688) or attending HIV testing centres (n=885); campaign managers (n=9); and campaign staff (n=38) or further intermediaries (n=80) in an online survey. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome measure was the proportion of MSM at risk of HIV acquisition or transmission who adhered to the campaign message. Secondary outcomes were postcampaign test uptake, knowledge about HIV primary infection and sense of belonging to the gay community. RESULTS Campaign staff estimated that they contacted 17 145 MSM in 11 cantons. Among 688 respondents to the postcampaign survey, 311 (45.2%) were categorised as MSM at risk. Of 402/688 (58.5%) MSM who had heard about Break the Chains 2015, MSM categorised as being at risk were less likely to report adherence to the campaign message than MSM not at risk (adjusted OR 0.24; 95% CI 0.14 to 0.42). Twenty per cent of MSM with a defined risk of HIV acquisition or transmission who adopted risk reduction declared having done so because of the campaign. Costs for one MSM at risk to adhere to the campaign message were estimated at USD purchasing power parity 36-55. The number of HIV tests in the month after the campaign was twice the monthly average. CONCLUSION Break the Chains increased HIV testing, implying that community-based campaigns are useful HIV prevention strategies for MSM. Additional interventions are needed to reach MSM at the highest risk of infection more effectively